1. Field of the Invention
The present invention relates generally to the field of therapeutic plasma perfusion to remove substances from blood. More particularly, the invention relates to methods and materials for removing free antigen and circulating immune complexes including such antigen from blood for therapeutic purposes.
Plasma perfusion has been performed to remove a variety of toxic and harmful substances from blood in a non-specific manner. The process involves removing blood from a patient, separating the cellular components from the plasma constituent, and passing the plasma through an immunoadsorbent column to remove the desired substances. The cellular blood components and treated plasma are then returned to the patient, either together or separately. Alternatively, the cellular components may be combined with other replacement plasma and reinfused into the patient. Particular applications have been the removal of poisons, overdosed drugs, cholesterol, immune complexes, autoimmune antibodies, rheumatoid factor, serum blocking factors, and the like.
Of particular interest to the present invention have been attempts to treat neoplastic diseases by the extracorporeal removal of circulating immune complexes from blood. Such complexes are formed by the binding of antigen to antibodies produced as a part of the humoral immune response to the antigen. It is thought that the formation of circulating immune complexes is part of the mechanism which turns off the immune response, in some cases prematurely. Removal of the immune complexes has usually been accomplished by binding the antibody component of the complex, typically using a protein-A immunoadsorbent material. Protein-A binds the F.sub.c region of certain subclasses of IgG, and the immunoadsorbent will thus non-specifically bind to the majority of circulating immune complexes in the blood, regardless of the nature of the antigen. While such treatments have lead to many examples of tumor regression, total remission of the tumor is rare.
For these reasons, it would be desirable to provide for improved methods and materials for treating neoplastic and other diseases by plasma perfusion. In particular, it would be desirable to provide materials and methods for removing particular antigens and circulating immune complexes from body fluids including such antigens in an antigen-specific manner.
2. Description of the Prior Art
U.S. Pat. No. 4,512,763 to Schneider discloses the use of an antibody immunoadsorbent for removing various components of a patient's blood, including immune complexes. Neither the feasibility nor the desirability of using antibodies specific for the antigen component of such complexes, however, is discussed. Plasma perfusion to remove circulating immune complexes by binding the F.sub.c region of the component antibody using protein-A is discussed in the following references: Kiprov et al. (1984) J. Biol. Res. Mod. 3:341-346; Jones et al. (1984) J. Biol. Res. Mod. 3:286-292; Besa et al. (1981) Am. J. Med. 71:1035-1040; European Patent Application 172 018 of Bensinger; European Patent Application 079 221 of Terman; and U.S. Pat. No. 4,614,513 to Bensinger.